- Microtubule and mitosis dynamics
- Photosynthetic Processes and Mechanisms
- Cellular transport and secretion
- Effects and risks of endocrine disrupting chemicals
- Protein Structure and Dynamics
- Carcinogens and Genotoxicity Assessment
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Toxic Organic Pollutants Impact
- Mitochondrial Function and Pathology
- Cancer-related Molecular Pathways
- Advanced Proteomics Techniques and Applications
- Nuclear Structure and Function
- Connexins and lens biology
- Protist diversity and phylogeny
- Educational and Psychological Assessments
- Electrostatic Discharge in Electronics
- Chemical and Physical Studies
- Pharmacogenetics and Drug Metabolism
- Railway Engineering and Dynamics
- Mineral Processing and Grinding
- Environmental Chemistry and Analysis
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
University of Oxford
2013-2024
National Center for Environmental Assessment (EPA)
1993-2010
Environmental Protection Agency
1981-2010
Santa Clara University
2008
Environmental Protection Agency
2008
Procter & Gamble (United States)
2001
University of Cincinnati Medical Center
1970
PP2A-B55 is one of the major phosphatases regulating cell division. Despite its importance for temporal control during mitotic exit, how B55 substrates are recognized and differentially dephosphorylated unclear. Using phosphoproteomics combined with kinetic modeling to extract B55-dependent rate constants, we have systematically identified assigned their order in exit. These share a bipartite polybasic recognition determinant (BPR) flanking Cdk1 phosphorylation site. Experiments show that...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation and preliminary characterization of purified ovalbumin messenger RNA from the hen oviductJeffrey M. Rosen, Savio L. C. Woo, James W. Holder, Anthony R. Means, Bert O'MalleyCite this: Biochemistry 1975, 14, 1, 69–78Publication Date (Print):January 1975Publication History Published online1 May 2002Published inissue 14 January 1975https://pubs.acs.org/doi/10.1021/bi00672a012https://doi.org/10.1021/bi00672a012research-articleACS...
Cytokinesis follows separase activation and chromosome segregation. This order is ensured in budding yeast by the mitotic exit network (MEN), where Cdc14p dephosphorylates key conserved Cdk1-substrates exemplified anaphase spindle-elongation protein Ase1p. However, metazoans, MEN Cdc14 function not conserved. Instead, PP2A-B55α/ENSA/Greatwall (BEG) pathway controls human Ase1p ortholog PRC1. In this pathway, PP2A-B55 inhibition coupled to Cdk1-cyclin B activity, whereas maintained cyclin...
Centrosomes comprise a pair of centrioles surrounded by pericentriolar material (PCM). The PCM expands dramatically as cells enter mitosis, but it is unclear how this occurs. In study, we show that the centriole protein Asl initiates recruitment DSpd-2 and Cnn to mother centrioles; both proteins then assemble into co-dependent scaffold-like structures spread outwards from recruit most, if not all, other components. absence either or Cnn, mitotic assembly diminished; in proteins, appears be...
ARH3/ADPRHL2 and PARG are the primary enzymes reversing ADP-ribosylation in vertebrates, yet their functions vivo remain unclear. ARH3 is only hydrolase able to remove serine-linked mono(ADP-ribose) (MAR) but much less efficient than against poly(ADP-ribose) (PAR) chains vitro. Here, by using ARH3-deficient cells, we demonstrate that endogenous MARylation persists on chromatin throughout cell cycle, including mitosis, surprisingly well tolerated. Conversely, persistent PARylation highly...
Cyclin B–dependent kinase (CDK1-CCNB1) promotes entry into mitosis. Additionally, it inhibits mitotic exit by activating the spindle checkpoint. This latter role is mediated through phosphorylation of checkpoint MPS1 and other proteins. We find that CDK1-CCNB1 localizes to unattached kinetochores like lost from these structures upon microtubule attachment. suggests an integral component not only upstream regulator pathway. Complementary proteomic cell biological analysis demonstrate protein...
Spindle checkpoint signaling is initiated by recruitment of the kinase MPS1 to unattached kinetochores during mitosis. We show that CDK1-CCNB1 and a counteracting phosphatase PP2A-B55 regulate engagement human with controlling phosphorylation status S281 in kinetochore-binding domain. This regulation essential for signaling, since MPS1S281A not recruited fails support other proteins. Directly tethering kinetochore protein Mis12 bypasses this hence requirement signaling. At metaphase–anaphase...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetermination of secondary structure in rabbit globin messenger RNA by thermal denaturationJames W. Holder and Jerry B. LingrelCite this: Biochemistry 1975, 14, 19, 4209–4215Publication Date (Print):September 23, 1975Publication History Published online1 May 2002Published inissue 23 September 1975https://pubs.acs.org/doi/10.1021/bi00690a009https://doi.org/10.1021/bi00690a009research-articleACS PublicationsRequest reuse permissionsArticle...
Centrosomes are the major microtubule-organizing centers in animals and play fundamental roles many cellular processes. Understanding how their composition varies across diverse cell types it is altered disease unresolved questions, yet currently available centrosome isolation protocols cumbersome time-consuming, they lack scalability. Here, we report development of affinity capture (CAPture)-mass spectrometry (MS), a powerful one-step purification method to obtain high-resolution proteomes...
The secondary structure of highly purified ovalbumin mRNA was studied by automated thermal denaturation techniques and the data were subjected to computer processing. Comparative studies with 20 natural synthetic model nucleic acids suggested that possesses following features: extent base pairing is similar found in tRNAs or ribosomal RNAs; more thermolabile than any compounds tested, including copolymer poly(A-U); does not have extensive G-C rich stems as composition double-stranded regions...
Cyclin B destruction is the crucial event triggering exit from mitosis. This study shows how PP1 promotes cyclin by removing inhibitory phosphorylation APC/C coactivator CDC20.
APC/C-mediated proteolysis of cyclin B and securin promotes anaphase entry, inactivating CDK1 permitting chromosome segregation, respectively. Reduction activity relieves inhibition the CDK1-counteracting phosphatases PP1 PP2A-B55, allowing wide-spread dephosphorylation substrates. Meanwhile, continued APC/C other mitotic regulators. Together, these activities orchestrate a complex series events during exit. However, relative importance regulated in dictating order timing remains unclear....
Abstract Aurora-A is an essential cell-cycle kinase with critical roles in mitotic entry and spindle dynamics. These functions require binding partners such as CEP192 TPX2, which modulate both activity localisation of Aurora-A. Here we investigate the structure role centrosomal Aurora-A:CEP192 complex wider molecular network. We find that wraps around Aurora-A, occupies sites for spindle-associated partners, thus competes them. Comparison two different conformations reveals how modifies...
Abstract Propiogenic substrates and gut bacteria produce propionate, a post-translational protein modifier. In this study, we used mouse model of propionic acidaemia (PA) to study how disturbances propionate metabolism result in histone modifications changes gene expression that affect cardiac function. Plasma surrogates were raised PA mice, but female hearts manifested more profound acyl-CoAs, propionylation acetylation, transcription. These resulted moderate diastolic dysfunction with Ca...
Chloroethane was observed in a chronic cancer bioassay to be mouse-specific uterine carcinogen at single high inhaled concentration (15,000 ppm). Although incidence occurred the female mouse (86%), no tumor increases were rats. is weak alkylating agent and has low acute toxicity. No genotoxicity potential been below 40,000 ppm. eliminated from body by pulmonary exhalation metabolically oxidation via cytochrome P-450 (likely producing acetaldehyde) conjugation with glutathione (GSH). The mode...
Flour and biscuit samples from a school lunch program were analyzed for ethylene dibromide (EDB). extracted with hexane at room temperature maximum extraction of EDB in 4 days. Biscuits by steam distillation hexane; optimum recoveries obtained triple the sample. Recoveries flour biscuits ranged 85 to 103% as determined gas-liquid chromatography on 15% OV-17 column 63Ni electron capture detector. Random confirmed gas chromatography-mass spectrometry. From less than 8 ppb ppm 0.5 260 biscuits....
ABSTRACT APC/C-mediated proteolysis of cyclin B and securin promotes entry into anaphase, inactivating CDK1 permitting chromosome segregation, respectively. Reduction activity relieves inhibition the CDK1-opposing phosphatases PP1 PP2A-B55 leading to dephosphorylation substrates crucial for mitotic exit. Meanwhile, continued APC/C is required target various proteins, including Aurora Polo kinases, degradation. Together, these activities orchestrate a complex series events during However,...